Multicenter evaluation of a fully automated high-throughput SARS-CoV-2 antigen immunoassay

Abstract

Background: Molecular testing for SARS-CoV-2 continues to suffer from delays and shortages. Antigen tests have recently emerged as a viable alternative to detect patients with high viral loads, associated with elevated risk of transmission. While rapid lateral flow tests greatly improved accessibility of SARS-CoV-2 detection in critical areas, their manual nature limits scalability and suitability for large-scale testing schemes. The Elecsys® SARS-CoV-2 Antigen assay allows antigen immunoassays to be carried out on fully automated high-throughput serology platforms. Methods: A total of 3139 nasopharyngeal and oropharyngeal swabs were collected at 3 different testing sites in Germany. Swab samples were pre-characterized by RT-qPCR and consecutively subjected to the antigen immunoassay on either the cobas e411 or cobas e801 analyzers. Results: Of the tested respiratory samples, 392 were PCR positive for SARS-CoV-2 RNA. Median concentration was 2.95×104 (interquartile range [IQR] 5.1×102–3.5×106) copies/mL. Overall sensitivity and specificity of the antigen immunoassay were 60.5% (95% confidence interval [CI] 55.5–65.4) and 99.9% (95% CI 99.6–100), respectively. A 93.7% (95% CI 89.7–96.5) sensitivity was achieved at a viral RNA concentration ≥104 copies/mL (cycle threshold (Ct) value <29.9). Conclusion: The Elecsys SARS-CoV-2 Antigen assay reliably detected patient samples with viral loads of 10,000 copies/mL and higher. It thus represents a viable high-throughput alternative for pre-screening of patients, or in situations where PCR testing is not readily available.

Accuracy of novel antigen rapid diagnostics for SARS-CoV-2: A living systematic review and meta-analysis

“…At the end of the data extraction process, 37 studies were still in preprint form [4,171,173,174,177,180,190,192,201,204,205,207,211,[214][215][216]218,220,222,223,225,227,231,233,234,238,240,244,247,253,257,265,267,284,287,290,293]. All studies were written in English, except for 2 in Spanish [175,280].…”

The accuracy of novel antigen rapid diagnostics for SARS-CoV-2: a living systematic review and meta-analysis

“…At the end of the data extraction process, 37 studies were still in preprint form [4,171,173,174,177,180,190,192,201,204,205,207,211,214–216,218,220,222,223,225,227,231,233,234,238,240,244,247,253,257,265,267,284,287,290,293]. All studies were written in English, except for two in Spanish [175, 280].…”

A method comparison study of the high throughput automated HISCL® SARS‐CoV‐2 antigen assay using nasopharyngeal swab samples from symptomatic and asymptomatic subjects against conventional RT‐PCR

“…still performed favorably (overall sensitivity 74.7%, total 1787 samples and 16.7% RT-PCR positivity) compared with other automated antigen assays where reported sensitivities ranged from 41.2% to 65.9%26,[28][29][30] overall, although all still falling short of the 80% sensitivity WHO recommendation 11. In a world without resource constraints, RT-PCR would be the test of choice for every testing situation, however, as resource availability is unequal, there is a…”

“…A recent study has suggested that antigen assays performed on high throughput immunoanalysers may offer a viable solution for patient screening, or in situations where RT-PCR testing is not readily available. 26 In this present study, we evaluated the performance of the au- handling error, rather than loss of assay sensitivity for the mutant antigen as 21/22 such mutants were correctly detected (Figure 2).…”

“…93.7%, 95% CI 89.7-96.5) at viral RNA concentrations of ≥ 10 4 copies/ml, equivalent to approximately C t < 29.9 26. Unlike RT-PCR, antigen assays directly measure viral material in the sample without amplification, hence sensitivity is strongly influenced by the infection kinetics and resultant viral concentration in the upper respiratory tract 13.…”